Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCDBbZyMFNbGmGBrG34cGFzsMS0066-782X2020001100538abc.2019068310.36660/abc.20190683Artigo OriginalImpacto dos Índices Aterogênicos em Estenose do Enxerto de Veia Safena0000-0003-1913-4212YavuzFethi10000-0002-3579-3747KilicSalih10000-0001-7081-5799KaplanMehmet10000-0002-2798-7488YıldırımArafat10000-0001-9186-3642KucukosmanogluMehmet10000-0002-3895-1923DogdusMustafa2Health Sciences UniversityAdana Research and Training HospitalDepartment of CardiologyAdanaTurquiaHealth Sciences University, Adana Research and Training Hospital, Department of Cardiology, Adana - TurquiaUşak UniversityResearch and Training HospitalDepartment of CardiologyUşakTurquiaUşak University Research and Training Hospital, Department of Cardiology, Uşak – Turquia Correspondência: Fethi Yavuz • Health Sciences University, Adana Research and Training Hospital, Department of Cardiology, Adana, Turkey - Department of Cardiology - Kışla Mahallesi, Dr. Mithat Özsan Bulvarı, 4522. Sokak No:1, Yüreğir/Adana Adana 01220 – Turquia E-mail: fethiyavuz782@gmail.com
Contribuição dos autores
Concepção e desenho da pesquisa: Yavuz F; Obtenção de dados: Kaplan M, Yıldırım A; Análise e interpretação dos dados: Kaplan M, Yıldırım A, Dogdus M; Análise estatística: Kilic S; Obtenção de financiamento: Kucukosmanoglu M; Redação do manuscrito: Yavuz F; Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Yavuz F, Kilic S.
Potencial conflito de interesses
Declaro não haver conflito de interesses pertinentes.
280920200920201153538544031020190312201927122019 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ResumoFundamento
Os enxertos de veias safenas (EVS) são frequentemente usados em pacientes submetidos a cirurgia de revascularização do miocárdio (CRM).
Objetivos
Avaliar as relações entre índices aterogênicos e estenose de EVS. Métodos: No total, 534 pacientes (27,7% mulheres, com idade média de 65±8,4 anos) submetidos a CRM e angiografia coronariana eletiva foram incluídos no estudo. Pacientes com pelo menos uma estenose EVS ≥50% foram alocados ao grupo estenose EVS (+) (n=259) e pacientes sem estenose foram classificados como EVS (-) (n=275). O índice aterogênico plasmático (IAP) e o coeficiente aterogênico (CA) foram calculados a partir dos parâmetros lipídicos de rotina dos pacientes. A significância foi estabelecida no nível p<0,05.
Resultados
O número de pacientes com histórico de hipertensão (HT), diabetes mellitus (DM), acidente vascular cerebral e insuficiência cardíaca (IC) se mostrou significativamente maior no grupo EVS (+) do que no grupo EVS (-). O colesterol total, triglicerídeos e colesterol LDL mostraram-se significativamente mais altos e o colesterol HDL mostrou-se menor no grupo EVS (+) do que no grupo EVS (-). IAP (p<0,001) e CA (p<0,001) apresentaram-se significativamente mais altos no grupo EVS (+) do que no grupo EVS (-). A análise ROC mostra que tanto o IAP quanto o CA mostraram-se melhores que o colesterol HDL, colesterol LDL e colesterol não HDL na predição de estenose de EVS. Na análise multivariada, histórico de DM, HT, acidente vascular cerebral, IC, número de enxertos de safena, colesterol HDL, colesterol LDL, colesterol não HDL, IAP e CA foram fatores de risco independentes para estenose de EVS.
Conclusão
O IAP e o CA foram preditores independentes de estenose de EVS. Além disso, tanto o IAP quanto o CA têm melhor desempenho na predição de estenose de EVS do que o colesterol LDL, colesterol HDL e colesterol não HDL. (Arq Bras Cardiol. 2020; 115(3):538-544)
Embora a cirurgia de revascularização do miocárdio (CRM) tenda a usar enxertos arteriais, os enxertos de veias safenas (EVS) ainda são frequentemente utilizados, principalmente em situações de emergência e em lesões de múltiplos vasos.1 O EVS tende a degenerar com o tempo. A deficiência de EVS limita o sucesso a longo prazo da cirurgia de revascularização miocárdica. As taxas de patência no 1º, 5º e no 10º ano após a CRM foram 93%, 74% e 41%, respectivamente.2
As principais causas de deficiência de EVS são trombose no período inicial (<1 mês), hiperplasia neointimal no período subagudo (1–12 meses) e aterosclerose no período tardio.3-5
Sabe-se que os níveis lipídicos séricos estão fortemente associados à aterosclerose.6 Níveis elevados de colesterol de lipoproteína de alta densidade (colesterol HDL) proporcionam um efeito cardioprotetor, enquanto níveis elevados de colesterol de lipoproteína de baixa densidade (colesterol LDL) são aterogênicos. Além disso, muitos estudos demonstraram que altos níveis de triglicerídeos (TG) estão associados à doença arterial coronariana (DAC).7-9 No entanto, a relação entre aumento dos parâmetros lipídicos e aumento do risco de doença arterial coronariana (DAC) permanece controversa. Estudos anteriores que mostram a associação entre colesterol e aterosclerose foram realizados usando os níveis de colesterol total (CT) e LDL-C. Quando do surgimento do papel do colesterol HDL como agente cardioprotetor, o uso da razão colesterol LDL/colesterol HDL foi recomendado para determinar o risco de DAC. Como os efeitos dos níveis séricos elevados de TG na aterosclerose estão claramente definidos, essa razão tem valor limitado, pois não inclui os níveis de TG.10
É importante ressaltar que diversas razões de lipoproteínas ou índices aterogênicos podem ser usados para otimizar a capacidade preditiva do perfil lipídico. Estudos demonstraram que os índices lipídicos calculados a partir dos parâmetros do perfil lipídico apresentam melhor valor preditivo em doenças cardiovasculares.11 O colesterol não HDL é recomendado como um preditor mais provável de DAC do que o colesterol LDL, porque representa o teor de colesterol encontrado em todas as lipoproteínas aterogênicas.12 O índice aterogênico plasmático (IAP) é calculado por meio de dois parâmetros importantes: TG sérico e colesterol HDL sérico. O uso simultâneo de triglicerídeos e colesterol HDL para essa razão reflete múltiplas interações entre o metabolismo de diferentes lipoproteínas e pode ser útil para predizer a aterogenicidade plasmática.13 Outro índice é o coeficiente aterogênico (CA) calculado como a razão entre colesterol não HDL e HDL.14 Até onde sabemos, a associação de índices aterogênicos plasmáticos com doença de EVS não foi estudada. Neste estudo, investigamos a relação entre os parâmetros lipídicos e os índices aterogênicos IAP e CA na estenose de EVS.
Materiais e Métodos
O estudo incluiu 534 pacientes (27,7% mulheres, n=148) submetidos a angiografia coronariana eletiva por mais de um ano (média de 5,3 anos) após a cirurgia de revascularização miocárdica, que envolveu pelo menos um EVS para bypass. Os pacientes foram divididos em dois grupos de acordo com a extensão da patência do EVS. Estenose de 50% ou mais, dentro do EVS, foi categorizada como estenose de EVS (+).
O comitê de ética local aprovou o protocolo deste estudo, conduzido de acordo com os princípios estabelecidos na Declaração de Helsinque (22/05/2019).
As características clínicas e demográficas basais da população do estudo foram registradas no formulário preparado para cada paciente. Todos os parâmetros laboratoriais de rotina antes da angiografia coronariana, laudo ecocardiográfico, peso, altura e índice de massa corporal (IMC) foram registrados no sistema digital do hospital. Calculou-se o IMC como peso/altura (m2). A hipertensão foi definida como medidas sistêmicas repetidas da pressão arterial que excederam 140/90 mmHg ou se o paciente estivesse tomando medicação anti-hipertensiva. Diagnosticou-se diabetes mellitus (DM) de acordo com um dos seguintes critérios: (1) glicemia em jejum ≥126 mg/dL, (2) glicemia >200 mg/dL a qualquer momento, (3) histórico de DM ou pacientes sob medicação antidiabética. Definiu-se hipercolesterolemia como nível basal total de colesterol >200 mg/dL ou tratamento atual com estatinas e/ou agentes hipolipemiantes. Fumantes atuais foram os que relataram tabagismo regular nos 6 meses anteriores. Definiu-se histórico familiar de doença arterial coronariana como a presença de doença arterial coronariana em parente de primeiro grau masculino com idade <55 anos ou em parente de primeiro grau feminino com idade <65 anos.
Cálculo de Índices Aterogênicos
O colesterol não HDL foi calculado como a diferença entre colesterol total e colesterol de alta densidade (colesterol total sérico — HDL-C sérico).15
O IAP foi calculado como o logaritmo da razão sérica de triglicerídeos/colesterol HDL sérico.13,16
O coeficiente aterogênico (CA) foi calculado como a razão entre colesterol não HDL e HDL, da seguinte forma: (colesterol sérico total — HDL-C sérico)/colesterol HDL).14
Avaliação Angiográfica
A angiografia coronariana foi realizada rotineiramente pela técnica de Judkins, com 6 ou 7 cateteres cardíacos franceses direito e esquerdo. Os angiogramas foram gravados em mídia digital DICOM a 25 quadrados/ms e foram revisados por dois angiógrafos experientes que desconheciam o estado clínico dos pacientes. Os enxertos de veias safenas foram vistos a partir de pelo menos dois ângulos após injeção seletiva de material de contraste. Definiu-se doença de enxerto venoso como estenose de 50% do diâmetro do vaso em qualquer EVS.
Análise Estatística
Variáveis contínuas com distribuição normal foram descritas como média ± desvio padrão (DP) e variáveis sem distribuição normal foram descritas como mediana e intervalo interquartil. As variáveis categóricas são apresentadas como o número de pacientes e porcentagens. As variáveis foram investigadas pelo método analítico de Kolmogorov-Smirnov para determinar se apresentam distribuição normal ou não. Realizou-se teste t de Student não pareado para variáveis com distribuição normal e o teste U de Mann-Whitney para aquelas sem distribuição normal. Para as variáveis categóricas, utilizou-se o teste do qui-quadrado ou o exato de Fisher. O tamanho da amostra da população do estudo não foi calculado e todos os pacientes consecutivos em nossa clínica foram incluídos no estudo.
Foram utilizadas curvas receiver operating characteristic (ROC) para demonstrar a sensibilidade e especificidade dos índices e lipídios, e seus valores de corte para prever estenose de EVS. A área sob a curva (AUC) desses índices aterogênicos e lipídios foi calculada pelo método DeLong.17 Para calcular as hazard ratios (HR) e seus intervalos de confiança de 95% (IC 95%) para estenose de EVS, realizou-se análise de regressão logística univariada e multivariável. Valores de p<0,05 foram considerados estatisticamente significativos. Os dados foram analisados utilizando o software estatístico SPSS, versão 20.0 (SPSS Inc., Chicago, IL, EUA) e o software estatístico MedCalc 15 (Ostend, Bélgica).
Resultados
No total, 534 pacientes (idade média de 65±8,4 anos) foram incluídos no estudo. Desse número, 259 (48,5%) foram diagnosticados com estenose de EVS (EVS (+)) e 275 (51,5%) foram diagnosticados com patência de EVS (EVS (-)). As características demográficas e clínicas basais dos grupos estudados estão resumidas na Tabela 1. O número de pacientes com histórico de HT, DM, acidente vascular cerebral e insuficiência cardíaca se mostrou significativamente maior no grupo estenose EVS (+) do que no grupo estenose EVS (-). A pressão arterial sistólica média e o número de enxertos foram maiores no grupo estenose EVS (+) do que no grupo estenose EVS (-). A fração de ejeção ventricular esquerda foi menor no grupo estenose EVS (+) do que no grupo estenose SVG (-). Os parâmetros laboratoriais e os índices lipídicos dos grupos de pacientes são apresentados na Tabela 2. Os parâmetros lipídicos, i.e., colesterol total, triglicerídeos e colesterol LDL apresentaram-se significativamente maiores, e o colesterol HDL apresentou-se menor no grupo EVS (+) do que no grupo EVS (-). Os índices lipídicos, IAP, CA e colesterol não HDL mostraram-se significativamente mais altos no grupo estenose EVS (+) do que no grupo estenose EVS (-) (p<0,001, para todos).
– Comparação das características basais clínicas da população estudada
Variável
Estenose de EVS (+) (n=259)
Estenose de EVS (-) (n=275)
p
Idade, anos
65,9 ± 8,66
64,6 ± 8,22
0,071
Índice de massa corporal, kg/m2
28,1 ± 3,75
28,0 ± 4,70
0,709
Pressão arterial sistólica, mmHg
126,5 ± 17,55
123,0 ± 12,24
0,007
Pressão arterial diastólica, mmHg
75,2 ± 9,89
74,0 ± 8,38
0,141
Intervalo após a cirurgia, mês
67,5 ± 39,55
60,6 ± 29,53
0,171
Fração de ejeção ventricular esquerda, %
52,1 ± 9,48
55,8 ± 6,38
<0,001
Sexo feminino, % (n)
25,1 (65)
30,4 (83)
0,172
Hipertensão, % (n)
78,0 (202)
66,5 (183)
0,003
Diabetes mellitus, % (n)
62,5 (162)
46,5 (128)
<0,001
Hiperlipidemia, % (n)
77,6 (201)
76,2 (204)
0,356
Doença vascular periférica, % (n)
12,7 (33)
9,5 (26)
0,226
Acidente vascular cerebral, % (n)
17,8 (46)
8,7 (24)
0,002
Doença renal crônica, % (n)
3,9 (10)
2,9 (8)
0,542
Insuficiência cardíaca, % (n)
38,6 (100)
15,6 (43)
<0,001
Fibrilação atrial, % (n)
6,2 (16)
6,6 (18)
0,827
Número de enxertos
1,99 ± 0,7
1,7 ± 0,65
<0,001
Aspirina, % (n)
81,1 (210)
85,8 (236)
0,140
Inibidores de P2Y12, % (n)
32,4 (84)
29,5 (81)
0,457
Betabloqueadores, % (n)
87,6 (227)
85,1 (234)
0,391
IECA/BRA, % (n)
75,7 (196)
71,6 (197)
0,290
Estatina, % (n)
59,8 (155)
64,7 (178)
0,245
Diuréticos, % (n)
22,8 (59)
15,3 (42)
0,027
Trimetazidina, % (n)
24,3 (63)
27,3 (75)
0,437
Ranolazina, % (n)
17,8 (46)
18,9 (52)
0,732
Nitratos, % (n)
27,8 (72)
16,7 (46)
0,002
Bloqueadores de canais de cálcio, % (n)
18,9 (49)
19,6 (54)
0,834
IECA: Inibidor da enzima conversora da angiotensina; BRA: bloqueador do receptor de angiotensina.
– Comparação de parâmetros laboratoriais e índices lipídicos dos grupos de estudo
CA: Coeficiente aterogênico; IAP: Índice aterogênico plasmático; HDL: Lipoproteína de alta densidade, LDL: Lipoproteína de baixa densidade.
Para a predição de estenose de EVS, o valor de corte de 3,4<CA possui sensibilidade de 79,15% e especificidade de 66.18%; o valor de corte de 0.56<IAP possui 83,01% de sensibilidade e 67,53% de especificidade; colesterol HDL<40 mg/dL possui 64,9% de sensibilidade e 84,0% de especificidade; 121 mg/dL<colesterol LDL possui 78,4% de sensibilidade e 58,9% de especificidade; e 141<colesterol não HDL possui 70,66% de sensibilidade e 54,55% de especificidade nas análises da curva ROC (Figura). Comparações pareadas da análise ROC mostram que, embora não houvesse diferenças significativas entre o IAP e o CA, tanto o IAP quanto o CA mostraram-se superiores ao colesterol HDL, colesterol LDL e colesterol não HDL na predição de estenose de EVAS.
– Curvas receiver operating characteristic (ROC) para estenose de EVS.
Para determinar os fatores de risco independentes para estenose de EVS, realizou-se análise logística univariada e multivariada (Tabela 3). Na análise multivariada, histórico de DM, HT, acidente vascular cerebral, IC, número de enxertos de safena, colesterol HDL, colesterol LDL e colesterol não HDL foram fatores de risco independentes para estenose de EVS. Além disso, os índices aterogênicos IAP e CA foram preditores independentes de estenose de EVS. Embora o nível de triglicerídeos tenha sido significativo na análise univariada, ele não alcançou significância estatística na análise multivariada.
Discussão
No presente estudo, observamos que fatores de risco cardiovascular tradicionais, como HT, DM, acidente vascular cerebral e insuficiência cardíaca, foram preditores independentes de estenose de EVS. Além disso, descobrimos que o colesterol HDL, colesterol LCL, colesterol não HDL, número de EVS e os índices aterogênicos IAP e CA foram preditores independentes de estenose de EVS. Além disso, observamos que o IAP e o CA têm melhor desempenho na predição de estenose de EVS do que o colesterol LDL, colesterol HDL e colesterol não HDL.
A estenose do enxerto de veia safena é uma questão importante no curto e no longo prazo dos pacientes submetidos a CRM, estando relacionada a grandes eventos cardiovasculares adversos. É importante identificar pacientes com alto risco de estenose de EVS para estratégias de prevenção e tratamento. Muitos fatores de risco relacionados à estenose de EVS, como fatores cirúrgicos, tabagismo, HT, HPL, DM, acidente vascular cerebral e outros, já foram determinados. Em seus estudos, Deppe et al. e Kim et al. mostraram que fatores cirúrgicos, como técnicas de aquisição de vasos ou uso de circulação extracorpórea, foram preditores independentes de estenose de EVS.18,19
O tabagismo é um fator de risco bem conhecido para aterosclerose e doença arterial coronariana.20-22 Sen et al. demonstraram que o tabagismo é um fator de risco independente para a doença de EVS em sua análise de regressão multivariada.20-22 Semelhante a estudos anteriores, demonstramos que o tabagismo é um importante fator de risco para estenose de EVS.
Demonstrou-se que a DM é uma das principais causas de aterosclerose em diversos estudos.23 A DM pode causar estenose de EVS como resultado de disfunção endotelial vascular causada por mecanismos fisiopatológicos imunes e não imunes.24 Koshizaka et al.,25 examinaram a relação entre DM e falha de enxerto avaliada por angiografia de um ano e desfecho clínico de cinco anos em pacientes submetidos a CRM. No estudo, observou-se que que a falha no EVS no primeiro ano foi semelhante entre pacientes com e sem DM. No entanto, óbito, infarto do miocárdio ou revascularização mostraram-se significativamente maiores em pacientes com DM com desfecho clínico de 5 anos.25 Em nosso estudo, histórico de DM foi considerado fator de risco independente para estenose de EVS.
A dislipidemia é um fator de risco bem conhecido para aterosclerose.23 Há evidências crescentes de que colesterol HDL baixo e colesterol LDL alto, colesterol total e triglicerídeos desempenham um papel na progressão da aterosclerose e doença arterial coronariana.26 Da mesma forma, demonstrou-se que colesterol HDL baixo com colesterol LDL alto está associado à estenose de EVS.27,28 Entre esses parâmetros, recomenda-se que o nível de colesterol LDL seja selecionado como alvo do tratamento.26 No entanto, após reduzir o colesterol LDL para os níveis recomendados, permanece um risco cardiovascular de ∼50%, motivando os pesquisadores a encontrarem novos preditores de arteriosclerose.29 Em comparação com os parâmetros lipídicos únicos, os índices lipídicos abrangentes, como IAP, CA e não HDL, são considerados melhores preditores de aterosclerose e doenças arteriais coronarianas.30,31
Em nosso estudo, semelhante a estudos anteriores, baixos níveis de colesterol HDL e altos níveis de colesterol LDL foram considerados fatores de risco independentes para estenose de EVS. Além disso, o alto nível de colesterol não HDL, outro fator de risco aterogênico, foi considerado um preditor independente de estenose de EVS.O colesterol não HDL não é o primeiro alvo na terapia hipolipemiante e pode ser um alvo secundário quando os pacientes atingem os níveis recomendados de colesterol LDL.26 Em nosso estudo, o nível médio de colesterol LDL dos pacientes foi superior aos valores recomendados para prevenção secundária. Isso mostra que os pacientes não receberam o tratamento hipolipemiante necessário e aqueles que o receberam não usaram doses efetivas para o colesterol LDL, que é o alvo principal.
Como se sabe, a LDL pequena e densa (sdLDL) pode se acumular e oxidar mais facilmente na parede do vaso em comparação com o colesterol LDL. Estudos anteriores mostraram que a sdLDL é um marcador que prediz a aterosclerose e pode ser usado clinicamente.26 No entanto, é complicado medir a sdLDL no sangue e seu alto custo limita seu uso clínico. O IAP obtido a partir do logaritmo TG/colesterol HDL reflete fortemente o equilíbrio entre lipoproteínas aterogênicas e protetoras. Um estudo anterior mostrou o IAP como inversamente relacionado ao diâmetro do colesterol LDL.32 Por esse motivo, o IAP pode ser usado como um fácil indicador na doença arterial coronariana. O IAP também pode ser rotineiramente calculado a partir de parâmetros lipídicos e usado como substituto do tamanho da partícula LDL sem ocasionar custos extras.
No presente estudo, observamos que o IAP é um indicador independente de estenose de EVS e apresentou melhor desempenho na predição de estenose de EVSA do que o colesterol LDL e o colesterol não HLD. Com base nesses resultados, mostramos que o IAP obtido por um cálculo simples pode ser usado para prever estenose de EVS. Em estudos anteriores, os valores médios do IAP diferiram.15,33-35 Essas diferenças podem dever-se à não homogeneidade de grupos de pacientes selecionados ou ao uso de fármacos. Outro motivo pode ser a diferença na carga de aterosclerose na população. No presente estudo, avaliamos apenas pacientes submetidos a CRM sob alto risco aterosclerótico. Como resultado, o valor médio do IAP do nosso estudo foi superior ao dos estudos publicados anteriormente.
O coeficiente aterogênico (CA) é uma medida de colesterol que utiliza frações de lipoproteínas LDL-C, VLDL-C e IDL-C em relação ao colesterol HDL.36
Ele reflete o potencial aterogênico de todo o espectro de frações de lipoproteínas. Como destacado acima, o colesterol não HDL é o segundo alvo da terapia após o colesterol LDL, de acordo com as diretrizes da ESC (European Society of Cardiology), principalmente em indivíduos com hipertrigliceridemia.26 Portanto, esse índice simples pode fornecer informações importantes para a identificação de indivíduos com risco de doença cardiovascular. Em nosso estudo, observamos que o CA médio mostrou-se significativamente maior no grupo estenose EVS (+) do que no grupo EVS (-) e foi preditor independente de estenose.
Além disso, o CA mostrou melhor desempenho na análise ROC do que o colesterol não HDL. Esse resultado mostra que o CA, que é um índice simples, deve ser considerado para prever estenose de EVS.
Limitações
O presente estudo apresenta algumas limitações. Primeiramente, trata-se de um estudo unicêntrico retrospectivo. No entanto, o número de pacientes é alto, o que aumenta o valor do estudo. Em segundo lugar, não comparamos os resultados com indivíduos controle saudáveis, o que poderia mostrar o valor normal do IAP e CA em nossa população saudável. Em terceiro lugar, como não houve desfechos clínicos no estudo, não é possível avaliar o impacto do IAP e do CA nos desfechos clínicos. Portanto, outros estudos são necessários para avaliar o impacto desses índices em pacientes submetidos a CRM.
Conclusão
No presente estudo, mostramos que HT, DM, acidente vascular cerebral, insuficiência cardíaca e colesterol HDL, colesterol LDL e colesterol não HDL foram preditores independentes de estenose de EVS, semelhante a estudos anteriores. Além disso, até onde sabemos, este é o primeiro estudo que mostra uma associação entre estenose de EVS e os índices aterogênicos IAP e CA. Além disso, observamos que os índices aterogênicos IAP e CA apresentam melhor desempenho na predição de estenose de EVS do que os parâmetros lipídicos padrão colesterol LDL, colesterol HDL e colesterol não HDL.
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JAMA. 2005;294(3):326-33.RidkerPMRifaiNCookNRBradwinGBuringJENon-HDL cholesterol, apolipoprotein A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in womenJAMA2005294332633312. Kinosian B, Glick H, Garland G. Cholesterol and coronary heart disease: predicting risks by levels and ratios. Ann Intern Med. 1994;121(9): 641-7.KinosianBGlickHGarlandGCholesterol and coronary heart disease: predicting risks by levels and ratiosAnn Intern Med1994121964164713. Cui Y, Blumenthal RS, Flaws JA, Whiteman MK, Langenberg P, Bachorik PS, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med. 2001;161(11):1413-9.CuiYBlumenthalRSFlawsJAWhitemanMKLangenbergPBachorikPSet alNon-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortalityArch Intern Med2001161111413141914. Wu J, Chen S, Liu L, Gao X, Zhou Y, Wang C, et al. 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Eur J Cardiothorac Surg. 2016;49(4):1031-41.DeppeACArbashWKuhnEWSlottoschISchernerMLiakopoulosOLet alCurrent evidence of coronary artery bypass grafting off-pump versus on-pump: a systematic review with meta-analysis of over 16,900 patients investigated in randomized controlled trialsEur J Cardiothorac Surg20164941031104119. Kim YH, Oh HC, Choi JW, Hwang HY, Kim KB. No-touch saphenous vein harvesting may improve further the patency of saphenous vein composite grafts: early outcomes and 1-year angiographic results. Ann Thorac Surg. 2017;103(5):1489-97.KimYHOhHCChoiJWHwangHYKimKBNo-touch saphenous vein harvesting may improve further the patency of saphenous vein composite grafts: early outcomes and 1-year angiographic resultsAnn Thorac Surg201710351489149720. Muir AD, McKeown PP, Bayraktutan U. Role of gender, smoking profile, hypertension, and diabetes on saphenous vein and internal mammary artery endothelial relaxation in patients with coronary artery bypass grafting. Oxid Med Cell Longev. 2010;3(3):199-205.MuirADMcKeownPPBayraktutanURole of gender, smoking profile, hypertension, and diabetes on saphenous vein and internal mammary artery endothelial relaxation in patients with coronary artery bypass graftingOxid Med Cell Longev20103319920521. Higman DJ, Greenhalgh RM, Powell JT. Smoking impairs endothelium-dependent relaxation of saphenous vein. Br J Surg. 1993;80(10):1242-5.HigmanDJGreenhalghRMPowellJTSmoking impairs endothelium-dependent relaxation of saphenous veinBr J Surg199380101242124522. Sen F, Yilmaz S, Balci KG, Sen O, Gül M, Çay S, et al. The relationship between vitamin D levels and saphenous vein graft patency. Coron Artery Dis. 2015;26(4):328-32.SenFYilmazSBalciKGSenOGülMÇaySet alThe relationship between vitamin D levels and saphenous vein graft patencyCoron Artery Dis201526432833223. 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Long-term clinical and angiographic outcomes in patients with diabetes undergoing coronary artery bypass graft surgery: results from the project of Ex-vivo Vein graft engineering via transfection IV trial. Am Heart J. 2015;169(1):175-84.KoshizakaMLopesRDReyesEMGibsonCMSchultePHafleyGEet alLong-term clinical and angiographic outcomes in patients with diabetes undergoing coronary artery bypass graft surgery: results from the project of Ex-vivo Vein graft engineering via transfection IV trialAm Heart J2015169117518426. Catapana AL, Graham I, Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis. 2016 Oct;253:281-344.CatapanaALGrahamIBackerGWiklundOChapmanMJDrexelHet al2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR)Atherosclerosis20161025328134427. Jerzewski K, Ruel M, Voisine P, May MR, Kulik A. Does high-density lipoprotein influence the development of saphenous vein graft disease after coronary bypass surgery?: exploratory analysis from the CASCADE trial. J Cardiothorac Surg. 2013 Jul 10;8:172.JerzewskiKRuelMVoisinePMayMRKulikADoes high-density lipoprotein influence the development of saphenous vein graft disease after coronary bypass surgery?: exploratory analysis from the CASCADE trialJ Cardiothorac Surg20130710817228. Hata M, Takayama T, Sezai A, Yoshitake I, Hirayama A, Minami K. Efficacy of aggressive lipid controlling therapy for preventing saphenous vein graft disease. Ann Thorac Surg. 2009;88(5):1440-4.HataMTakayamaTSezaiAYoshitakeIHirayamaAMinamiKEfficacy of aggressive lipid controlling therapy for preventing saphenous vein graft diseaseAnn Thorac Surg20098851440144429. Ridker PM, Rifai N, Rose RL, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557-65.RidkerPMRifaiNRoseRLBuringJECookNRComparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular eventsN Engl J Med2002347201557156530. Gao M, Zheng Y, Zhang W, Cheng Y, Wang L, Qin L. Non-high-density lipoprotein cholesterol predicts nonfatal recurrent myocardial infarction in patients with ST segment elevation myocardial infarction. Lipids Health Dis. 2017 Jan 23;16:20.GaoMZhengYZhangWChengYWangLQinLNon-high-density lipoprotein cholesterol predicts nonfatal recurrent myocardial infarction in patients with ST segment elevation myocardial infarctionLipids Health Dis20170123162031. Zhu L, Lu Z, Zhu L, Ouyang X, Yang Y, He W, et al. Lipoprotein ratios are better than conventional lipid parameters in predicting coronary heart disease in Chinese Han people. Kardiol Pol. 2015;73(10):931-8.ZhuLLuZZhuLOuyangXYangYHeWet alLipoprotein ratios are better than conventional lipid parameters in predicting coronary heart disease in Chinese Han peopleKardiol Pol2015731093193832. Frohlich J, Dobiasova M. Fractional esterification rate of cholesterol and triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography. Clin Chem. 2003;49(11):1873-80.FrohlichJDobiasovaMFractional esterification rate of cholesterol and triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiographyClin Chem200349111873188033. Nansseu JRN, Moor VJA, Nouaga MED, Zing-Awona-B, Tchanana G, Ketcha A. Atherogenic index of plasma and risk of cardiovascular disease among Cameroonian postmenopausal women. Lipids Health Dis. 2016 Mar 9;15:49.NansseuJRNMoorVJANouagaMEDZing-AwonaBTchananaGKetchaAAtherogenic index of plasma and risk of cardiovascular disease among Cameroonian postmenopausal womenLipids Health Dis2016039154934. Hartopo AB, Arso IA, Setianto BY. Low plasma atherogenic index associated with poor prognosis in hospitalized patients with acute myocardial infarction. Acta Med Indones. 2016;48(2):106-13.HartopoABArsoIASetiantoBYLow plasma atherogenic index associated with poor prognosis in hospitalized patients with acute myocardial infarctionActa Med Indones201648210611335. 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Vinculação acadêmica
Não há vinculação deste estudo a programas de pós-graduação.
Fontes de financiamento
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Original ArticleImpact of Atherogenic Indexes in Saphenous Vein Graft Stenosis0000-0003-1913-4212YavuzFethi10000-0002-3579-3747KilicSalih10000-0001-7081-5799KaplanMehmet10000-0002-2798-7488YıldırımArafat10000-0001-9186-3642KucukosmanogluMehmet10000-0002-3895-1923DogdusMustafa2TurkeyHealth Sciences University, Adana Research and Training Hospital, Department of Cardiology, Adana - TurkeyTurkeyUşak University Research and Training Hospital, Department of Cardiology, Uşak – TurkeyMailing Address: Fethi Yavuz • Health Sciences University, Adana Research and Training Hospital, Department of Cardiology, Adana, Turkey - Department of Cardiology - Kışla Mahallesi, Dr. Mithat Özsan Bulvarı, 4522. Sokak. No:1, Yüreğir/Adana Adana 01220 – Turkey E-mail: fethiyavuz782@gmail.com
Author contributions
Conception and design of the research: Yavuz F; Acquisition of data: Kaplan M, Yıldırım A; Analysis and interpretation of the data: Kaplan M, Yıldırım A, Dogdus M; Statistical analysis: Kilic S; Obtaining financing: Kucukosmanoglu M; Writing of the manuscript: Yavuz F; Critical revision of the manuscript for intellectual content: Yavuz F, Kilic S.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
AbstractBackground
Saphenous vein grafts (SVG) are frequently used in patients that have undergone coronary artery bypass graft (CABG) surgery. Objectives: To evaluate the relationship between atherogenic indexes and SVG stenosis.
Methods
Altogether, 534 patients (27.7% women, mean age 65±8.4 years) that underwent CABG and elective coronary angiography were included in the study. Patients with at least one SVG stenosis ≥50% were allocated to the stenosis group SVG (+) (n=259) and patients without stenosis were categorized as SVG (-) (n=275). Atherogenic index of plasma (AIP) and atherogenic coefficient (AC) were calculated from the patients’ routine lipid parameters. The level of significance was p<0.05.
Results
The number of patients with a history of hypertension (HT), diabetes mellitus (DM), stroke, and heart failure was significantly higher in the SVG (+) group than in the SVG (-) group. Total cholesterol, triglycerides, LDL-C were significantly higher and HDL-C was lower in the SVG (+) group than in the SVG (-) group. AIP (p<0.001) and AC (p<0.001) were significantly higher in the SVG (+) group than in the SVG (-) group. The receiver operating characteristic (ROC) analysis show that both AIP and AC were better than HDL-C, LDL-C and non-HDL-C at predicting SVG stenosis. In the multivariate analysis, history of DM, HT, stroke, heart failure (HF), number of saphenous grafts, HDL-C, LDL-C, non-HDL-C, AIP and AC were found to be independent risk factors for SVG stenosis.
Conclusion
AIP and AC were independent predictors of SVG stenosis. Moreover, both AIP and AC have better performance in predicting SVG stenosis than LDL-C, HDL-C and non-HDL-C. (Arq Bras Cardiol. 2020; 115(3):538-544)
Although coronary artery bypass graft (CABG) surgery tends to use arterial grafts, saphenous vein grafts (SVG) are still frequently used, especially in emergency situations and in multiple vessel lesions.1 SVG tends to degenerate over time. SVG deficiency limits the long-term success of surgical coronary revascularization. Patency rates at the 1st, 5th and 10th years after CABG were reported to be 93%, 74% and 41%, respectively.2
The main causes of SVG deficiency are thrombosis in the early period (<1 month), neointimal hyperplasia in the subacute period (1–12 months) and atherosclerosis in the late period.3-5
Serum lipid levels are known to be strongly associated with atherosclerosis.6 Increased levels of high-density lipoprotein cholesterol (HDL-C) provide a cardioprotective effect while elevated low-density lipoprotein cholesterol (LDL-C) levels are atherogenic. In addition, many studies have shown that high triglyceride (TG) levels are associated with coronary artery disease (CAD).7-9 However, the relationship between increased lipid parameters and increased risk of coronary artery disease (CAD) remains controversial. Previous studies showing the association of cholesterol with atherosclerosis were performed using total cholesterol (TC) and LDL-C levels. When the role of HDL-C as a cardio-protective agent appeared, the use of the LDL-C/HDL-C ratio was recommended to determine the risk of CAD. Since the effects of high-serum TG levels on atherosclerosis are clearly defined, this ratio has a limited value since it does not include TG levels.10
Importantly, various lipoprotein ratios or atherogenic indexes can be used to optimize the predictive capacity of the lipid profile. Studies have shown that lipid indexes calculated from lipid profile parameters have a better predictive value in cardiovascular diseases.11 Non-HDL cholesterol (NHC) is recommended as a more likely predictor of CAD than LDL-C because it represents the cholesterol content found in all atherogenic lipoproteins.12 Atherogenic index of plasma (AIP) is calculated with two important parameters: serum TG and serum HDL-C. The simultaneous use of triglycerides and HDL-C for this ratio reflects multiple interactions between the metabolism of different lipoproteins and may be useful for predicting plasma atherogenicity.13Another index is the atherogenic coefficient (AC) calculated as the ratio of non-HDL cholesterol to HDL.14 To our knowledge, the association of plasma atherogenic indexes with SVG disease has not been studied. In this study, we investigated the relationship between lipid parameters and the atherogenic indexes AIP and AC in SVG stenosis.
Materials and Methods
The study consisted of 534 patients (27.7% women, n=148) who underwent elective coronary angiography more than one year (mean 5.3 years) after CABG surgery, which involved at least one SVG for bypass. The patients were divided into two groups according to the extent of SVG patency. Stenosis of 50% or greater within the SVG was categorized as SVG (+) stenosis.
The local ethics committee approved the protocol of this study, which was conducted according to the principles established in the Declaration of Helsinki (22/05/2019).
Baseline clinical and demographic characteristics of the study population were recorded in the form that was prepared for each patient. All routine laboratory parameters before coronary angiography, echocardiography report, weight, height and body mass index (BMI) were recorded from the digital system of the hospital. BMI was calculated as weight/height (m)2. Hypertension was defined as repeated systemic blood pressure measurements exceeding 140/90 mmHg or if the patient was taking anti-hypertensive medication. Diabetes mellitus (DM) was diagnosed according to one of the following criteria: (1) fasting blood glucose ≥126 mg/dL, (2) blood glucose >200 mg/dL at any time, (3) history of DM or patients on anti-diabetic medication. Hypercholesterolemia was defined as baseline total cholesterol level >200 mg/dL or current treatment with statins and/or lipid-lowering agents. Current smokers were those reporting regular smoking in the previous 6 months. Family history of coronary artery disease was defined as the presence of coronary artery disease in a male first-degree relative aged <55 years or in a female first-degree relative aged <65 years.
Calculation of atherogenic indexes
Non-HDL was calculated as the difference between total cholesterol and high-density cholesterol (serum total cholesterol — serum HDL-C).15
AIP was calculated as the logarithm of serum triglyceride/serum HDL-C ratio.13,16
Atherogenic coefficient (AC) was calculated as the ratio of non-HDL cholesterol to HDL cholesterol, as follows: (total serum cholesterol — Serum HDL-C)/HDL-C).14
Angiographic evaluation
Coronary angiography was routinely performed by the Judkins technique using 6 or 7 French right and left heart catheters. Angiograms were recorded on a DICOM digital media at 25 squares/msec and were reviewed by two experienced angiographers unaware of the patients’ clinical status. Saphenous vein grafts were viewed from at least two angles after selective injection of contrast material. Vein graft disease was defined as stenosis of 50% of the vessel diameter in any SVG.
Statistical analysis
Continuous variables with normal distribution were reported as mean ± standard deviation (SD) and variables without normal distribution were reported as median and interquartile range. Categorical variables were expressed as the number of patients and percentages. The variables were investigated using the analytic method of Kolmogorov-Smirnov to determine whether or not they are normally distributed. Unpaired Student’s t-test was performed for normally distributed variables and Mann-Whitney U test for those without normal distribution. Chi-square test or Fisher’s exact test was performed for the categorical variables. The sample size of the study population was not calculated and all consecutive patients in our clinic were included in the study.
Receiver operating characteristics (ROC) curves were used to demonstrate the sensitivity and specificity of the indexes and lipids, and their cut-off values for predicting SVG stenosis. The area under the curve (AUC) of these atherogenic indexes and lipids was calculated using the DeLong method.17 To calculate hazard ratios (HR) and their 95% confidence intervals (95% CIs) for SVG stenosis, univariate and multivariate logistics regression analysis was performed. A p value<0.05 was considered statistically significant. Data were analyzed using SPSS statistical software, version 20.0 (SPSS Inc., Chicago, IL, USA) and MedCalc 15 statistical software (Ostend, Belgium). (Quais índices? Sugiro especificar)
Results
A total of 534 patients (mean age 65±8.4 years) was included in the study. Of those, 259 (48.5%) were diagnosed with a stenotic SVG (SVG (+)) and 275 (51.5%) were diagnosed as patency SVG (SVG (-)). Baseline demographic and clinical characteristics of study groups are summarized in Table 1. The number of patients with a history of HT, DM, stroke, and heart failure were significantly higher in the SVG (+) stenosis group than in the SVG (-) stenosis group. Mean systolic blood pressure and number of grafts were higher in the SVG (+) stenosis group than in the SVG (-) stenosis group. Left ventricular ejection fraction was lower in the SVG (+) stenosis group than in the SVG (-) stenosis group. Laboratory parameters and lipid indexes of the patient groups are presented in Table 2. Lipid parameters, meaning, total cholesterol, triglycerides and LDL-C were significantly higher, and HDL-C was lower in the SVG (+) group than in the SVG (-) group. The lipid indexes, AIP, AC, and non-HDL-C were significantly higher in the SVG (+) stenosis group than in the SVG (-) stenosis group (p<0.001, for all).
– Comparison of baseline characteristics of the study population
– Comparison of laboratory parameters and lipid indexes of the study groups
Variable
SVG disease (+) (n=259)
SVG disease (-) (n=275)
p
Hba1c, %
7.2 ± 1.9
7.0 ± 2.0
0.296
Fasting glucose level, mg/dL
174 ± 108
164 ± 94
0.249
Hemoglobin, g/dL
13.2 ± 1.64
13.1 ± 1.84
0.205
Hematocrit, %
39.1 ± 4.82
38.6 ± 4.97
0.259
White blood cell count, x103/mL
8.7 ± 2.26
8.5 ± 2.1
0.553
Platelet count, x103/mL
244 ± 68
237 ± 65
0.206
Neutrophil count, x103/mL
5.5 ± 1.78
5.3 ± 1.93
0.307
Lymphocyte count, x103/mL
2.1 ± 0.8
2.1 ± 0.7
0.377
Monocyte count, x103/mL
0.7 ± 0.21
0.7 ± 0.26
0.860
Mean platelet volume, fL
8.8 ± 0.96
9.9 ± 1.12
0.123
Red cell distribution width, fL
15.7 ± 2.71
14.7 ± 2.14
0.182
Total cholesterol, mg/dL, median (25th–75th percentile)
201 (174–232)
185.0 (165–222)
0.001
LDL-Cholesterol, mg/dL
137.0 ± 34.7
126.8 ± 37.2
0.001
HDL-Cholesterol, mg/dL, median (25th–75th percentile)
37.0 (34.0–43.0)
48.0 (42–54.5)
<0.001
Triglycerides, mg/dL, median (25th–75th percentile)
203 (156–273)
143.0 (111–189.5)
<0.001
Urea, mg/dL, median (25th–75th percentile)
37.0 (29.0–47.0)
37.0 (29.0–42.0)
0.621
Creatine, mg/dL, median (25th–75th percentile)
0.90 (0.70.–1.10)
0.80 (0.70–1.0)
0.253
Albumin, mg/dL
3.8 ± 0.49
3.9 ± 0.38
0.174
Alanine transaminase, U/L
19.1 ± 2.93
19.0 ± 3.17
0.899
Aspartate aminotransferase, U/L
23.2 ± 3.61
24.2 ± 3.94
0.966
Serum uric acid, mg/dl
5.7 ± 1.6
5.4 ± 1.7
0.172
AIP
0.73 ± 0.20
0.50 ± 0.23
<0.001
AC
4.44 ± 1.30
3.08 ± 1.06
<0.001
Non-HDL cholesterol
165.7 ± 42.74
144.6 ± 44.44
<0.001
AC: Atherogenic coefficient; AIP: Atherogenic index of plasma; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; Non-HDL cholesterol: Non-high-density lipoprotein cholesterol.
For the prediction of SVG stenosis, the cut-off value of 3.4<AC has 79.15% sensitivity and 66.18% specificity; cut-off value of 0.56<AIP has 83.01% sensitivity and 67.53% specificity; HDL-C<40 mg/dL has 64.9% sensitivity and 84.0% specificity; 121 mg/dL<LDL-C has 78.4% sensitivity and 58.9% specificity; and 141<non-HDL cholesterol has 70.66% sensitivity and 54.55% specificity in the ROC curve analyses (Figure). Paired comparisons of ROC analysis show that, although there were no significant differences between AIP and AC, both AIP and AC were better than HDL-C, LDL-C and non-HDL-C at predicting SVG stenosis.
– Receiver operating characteristic (ROC) curves for SVG stenosis.
To determine the independent risk factors for SVG stenosis, univariate and multivariate logistic analysis was performed (Table 3). In the multivariate analysis, history of DM, HT, stroke, HF, number of saphenous grafts, HDL-C, LDL-C and non-HDL-C were found to be independent risk factors for SVG stenosis. Moreover, the atherogenic indexes, AIP and AC were found to be independent predictors of SVG stenosis. Although the triglyceride level was significant in univariate analysis, it did not achieve statistical significance in the multivariate analysis.
Discussion
In the present study, we found that traditional cardiovascular risk factors such as HT, DM, stroke and heart failure were independent predictors of SVG stenosis. Also, we found that HDL-C, LCL-C, non-HDL-C, the number of SVGs and the atherogenic indexes AIP and AC were independent predictors of SVG stenosis. Moreover, we found that API and AC have better performance to predict SVG stenosis than LDL-C, HDL-C and non-HDL-C.
Saphenous vein graft stenosis is a major issue in the short-term and long-term of CABG patients and is related to major adverse cardiovascular events. It is important to identify patients at high risk of SVG stenosis for prevention and treatment strategies. Many risk factors related to SVG stenosis such as surgery-related factors, smoking, HT, HPL, DM, stroke and others have been determined previously. In their studies, Deppe et al. and Kim et al. have shown that surgery-related factors such as vein acquisition techniques or use of extracorporeal circulation were independent predictors of SVG stenosis.18,19 (Descrever sigal)
Smoking is a well-known risk factor for atherosclerosis and coronary artery disease.20-22 Sen et al. have shown that smoking is an independent risk factor for SVG disease in their multivariate regression analysis.20-22 Similar to previous studies, we have shown that smoking is an important risk factor of SVG stenosis.
DM has been shown to be a major cause of atherosclerosis in many studies.23 DM can cause SVG stenosis as a result of vascular endothelial dysfunction caused by immune and non-immune pathophysiological mechanisms.24 Koshizaka et al.25 examined the relationship between DM and graft failure assessed by one-year angiography and 5-year clinical outcome in CABG patients. In this study, they found that SVG failure in the first year was similar between patients with and without DM. However, death, myocardial infarction or revascularization were found to be significantly higher in DM patients at 5-year clinical outcome.25 In our study, history of DM was found to be an independent risk factor for SVG stenosis.
Dyslipidemia is a well-known risk factor for atherosclerosis.23 There is increasing evidence that low HDL-C and high LDL-C, total cholesterol and triglycerides play a role in the progression of atherosclerosis and coronary artery disease.26 Similarly, low HDL-C with high LDL-C has been shown to be associated with SVG stenosis.27,28 Among these parameters, LDL-C level should be recommended to be selected as a treatment target.26 However, after reducing LDL-C to the recommended levels, 50% remnant cardiovascular risk remains, thus encouraging researchers to find new arteriosclerosis predictors.29 Compared to the single lipid parameters, the comprehensive lipid indexes, such as AIP, AC and non-HDL, are considered to be better predictors of atherosclerosis and coronary artery diseases.30,31
In our study, similar to previous studies, low HDL-C and high LDL-C levels were found to be independent risk factors for SVG stenosis. In addition, high level of non-HDL-C, another atherogenic risk factor, was found to be an independent predictor of SVG stenosis. Non-HDL-C is not the first target in lipid-lowering therapy and it may be a secondary target when patients reach recommended LDL-C levels.26 In our study, the mean LDL-C level of the patients was found to be above the recommended values for secondary prevention. This shows that patients did not receive the necessary lipid-lowering treatment, and those who received it did not use effective doses for LDL-C, which is the primary target.
As it is known, small density LDL (sdLDL) can accumulate and oxidize more easily on the vessel wall compared to LDL-C. Previous studies have shown that sdLDL is a marker that predicts atherosclerosis and can be used clinically.26 However, it is complicated to measure sdLDL in blood and its high cost limits its clinical use. AIP obtained from the TG/HDL-C logarithm strongly reflects the balance between atherogenic and protective lipoproteins. A previous study showed that AIP was inversely related to LDL-C diameter.32 For this reason, AIP can be used as an easy indicator in coronary artery disease. AIP can also be routinely calculated from lipid parameters and used as a surrogate of LDL particle size without causing extra costs.
In our study, we found that AIP is an independent indicator of SVG stenosis and had a better performance predicting SVG stenosis than LDL-C and non-HLD-C. Based on these results, we have shown that AIP obtained by a simple calculation can be used to predict SVG stenosis. In previous studies, average AIP values have differed.15,33-35 These differences may be due to the non-homogeneity of selected patient groups or drug use. Another reason may be the difference in the burden of atherosclerosis in the population. In our study, we only evaluated patients with CABG under high atherosclerotic risk. As a result, the mean AIP value of our study was higher than that of studies previously published.
Atherogenic Coefficient (AC) is a measure of cholesterol using LDL-C, VLDL-C, IDL-C lipoprotein fractions with respect to HDL-C.36
It reflects the atherogenic potential of the entire spectrum of lipoprotein fractions. As emphasized above, non-HDL-c is the second target of therapy after LDL-C as per the ESC (European Society of Cardiology) guidelines, especially in individuals with hypertriglyceridemia.26 Hence, this simple index could provide valuable information to identify subjects at risk for cardiovascular diseases. In our study, we found that mean AC was significantly higher in the SVG (+) stenosis group than in the SVG (-) group, and was an independent predictor of stenosis. Also, AC has shown better performance in ROC analysis than non-HDL. This result shows that AC, which is a simple index, should be considered to predict SVG stenosis.
Limitations
The present study has some limitations. Firstly, this is a retrospective single-center study. However, the number of patients is high, which increases the value of the study. Secondly, we did not compare the results with healthy control subjects, which could show the normal value of AIP and AC in our healthy population. Thirdly, because there were no clinical endpoints in the study, it is not possible to evaluate the impact of AIP and AC for clinical endpoints. Hence, other studies are needed to evaluate the impact of these indexes in CABG patients.
Conclusion
In the present study, we show that HT, DM, stroke, heart failure and HDL-C, LDL-C and non-HDL-C were independent predictors of SVG stenosis, similar to previous studies. Also, to the best of our knowledge, this is the first study which shows an association between SVG stenosis and the atherogenic indexes AIP and AC. Moreover, we have found that the atherogenic indexes AIP and AC have better performance in predicting SVG stenosis than standard lipid parameters LDL-C, HDL-C, and non-HDL-C.
Study Association
This study is not associated with any thesis or dissertation work.
Sources of Funding
There were no external funding sources for this study.